The brain protective effect of Ulinastatin in rats with deep hypothermic circulatory arrest

Li Kunyu; Gao Guodong; Hu Qiang

doi:10.13498/j.cnki.chin.j.ecc.2024.06.16

Abstract：Objective To explore the protective effect of ulinastatin on brain in rats receiving deep hypothermic circulatory arrest (DHCA). Methods 24 rats were randomly divided into the control group (Sham group),low-dose ulinastatin group (50,000 U/kg),medium-dose ulinastatin group (100,000 U/kg),high-dose ulinastatin group (200,000 U/kg),with 6 rats in each group. After establishing stable extracorporeal circulation in rats,the DHCA model is created with a target temperature of 18°C and a cardiac arrest duration of 45 minutes,and the rats were given corresponding dose ulinastatin through the femoral artery 15 minutes before the start of cardiopulmonary bypass and the termination of cardiopulmonary bypass,respectively. Blood gas analysis was performed before the start of cardiopulmonary bypass (T1),at the beginning of cardiopulmonary bypass (T2),10 minutes after resuming circulation (T3),immediately upon the end of cardiopulmonary bypass (T4),and 4 hours after the end of cardiopulmonary bypass (T5) .The contents of interleukin(IL)-6、interleukin(IL)-10、tumor necrosis factor(TNF)-α and S100-β in serum were measured by ELISA at T2、T4 and T5. And observe brain slices of hippocampus using light and transmission electron microscopy after the experiment. Results With the establishment of cardiopulmonary bypass and the recovery of spontaneous circulation in rats,the levels of IL-6,IL-10,TNF-α and S100-β gradually increased. Low dose of ulinastatin could alleviate the inflammatory response in the body of rats,reduce the levels of IL-6 and TNF-α in serum to a certain extent,and significantly reduce the level of S100-β (P<0.05);Medium and high dose of ulinastatin could significantly alleviate the inflammatory response in the body of rats,reduce the levels of IL-6,TNF-α and S100-β (P<0.05),increase the level of IL-10 in serum (P<0.05). Under a light microscope,as the drug dose increased,the cells in the rat hippocampus became more and more neatly arranged and there were fewer and fewer necrotic neurons. Under transmission electron microscopy,as the drug dose increased,the number of autophagosomes we observed was gradually decreased. Blood gas analysis showed that ulinastatin could reduce the levels of blood sugar and lactic acid in DHCA rats. Conclusion Ulinastatin can alleviate the inflammatory response in the body of rats undergoing deep hypothermic circulatory arrest,and has a certain brain protective effect which is dose-dependent within a certain range.